Breast Cancer

Brain metastases are formed when tumors originating from tissues outside the central nervous system metastasize and involve brain tissue. Brain metastases are the most common intracranial tumor in adults, and 13%-20% of brain metastases have breast cancer as the primary tumor, making breast cancer the second most common tumor-causing central nervous system metastasis after lung cancer.

The routes of breast cancer brain metastases (BCBM) include hematologic metastases, direct infiltration of cranial periphery and adjacent organ tissues and cerebrospinal fluid metastases, and lymphatic metastases. Biological risk factors associated with breast cancer pathology include the clinical grade of the tumor, estrogen receptor (ER) status, human epidermal growth factor receptor 2 status (HER2), and BRCA mutation status.

Figure 1. Peri-tumoral neural niche in brain metastasis from breast cancer. (Jandial, R., et al., 2016)

HER2-targeted therapy

HER2 is a membrane tyrosine kinase and is part of the EGFR family. HER2 is upregulated in brain metastases compared to primary tumors and is involved in the colonization of breast cancer cells in the brain. HER2 upregulation promotes cell survival and proliferation through a variety of downstream pathways and Alfa Cytology provides effective research solutions and technical support for HER2-positive brain metastases.

Monoclonal antibodies

• Small tyrosine kinase HER2 inhibitors
• Reversible inhibitors of HER2 and epidermal growth factor receptor (EGFR).
• Irreversible inhibitors of HER2 and inhibition of HER2 and HER3 mutations.
• Reversible HER2 inhibitors.
• Monoclonal antibodies against HER2
• HER2 inhibitors.
• Antibody-drug coupling.
• Various other targeted drugs
• CDK4/CDK6 inhibitors. Blocking downstream signaling pathways by inhibiting CDK4/CDK6 is a therapeutic strategy to counter drug resistance. Our solutions to help you understand the mechanisms of resistance to CDK4/CDK6 inhibitor therapy can help you develop and use drugs more specifically to counter CDK4/6 inhibitor resistance.
• PARP inhibitors.
• PI3K/Akt/mTOR inhibitors.
• VEGF pathway inhibitors.

Immune checkpoint inhibitors (ICIs)

The intracranial activity of ICIs may be explained by penetration of the brain through the damaged blood-brain barrier or meningeal lymphatics, or by the initiation and activation of anti-tumour T cells at extracerebral sites and return to the brain.

A research model for BCBM

Nanotherapy

Nanocarriers offer a unique advantage in drug delivery in that they have a high drug-loading capacity and protect the enclosed drug from being cleared too quickly. As a result, a concentration gradient is created, allowing passive diffusion of the drug through the tumor microvasculature. Nanoparticles can be combined with therapeutic agents that target overexpressed antigens or receptors and may be a promising therapeutic system.

Brain metastases progress rapidly, and since brain tissue is the "command" of the body, even a small tumor can have a significant impact on quality of life. The vast majority of systemic treatments are ineffective for BCBM, so local treatment of BCBM has become a critical part of the overall disease course and quality of life. Please feel free to contact Alfa Cytology for more research and information support.

Reference

1. Jandial, R., et al. (2016). "Peri-tumoral neural niche in brain metastasis from breast cancer." Integr Cancer Sci Therap, 3: DOI: 10.15761/ICST.1000199.